Cationic surfactant compounds are well-known in the art for their capacity to inhibit the formation of bacterial colonies.
This antimicrobial activity is described in detail in EP-A-0 749 960. The efficacy of the product lauramide of L-arginine ethyl ester monohydrochloride was proven against more microorganisms: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger. The product is further known to be efficaceous against the bacteria Alcaligenes faecalis, Bordetella bronchiseptica, Citrobacter freundii, Enterobacter aerogenes, Klebsiella pneumoniae spp. pneumoniae, Proteus mirabilis, Salmonelly thyphimurium, Serratia marcescens, Bacillus subtilus, Bacillus cereus spp. mycoide, Micrococcus luteus, Arthrobacter oxydans, Mycobacterium phlei and Listeria monocytogenes, against the yeasts Rhodotorula rubra, Saccharomyces cerevisiae and Zygosaccharomyces rouxii and and against the fungi Mucor rouxii, Aureobasidium pullulans, Chaetonium globosum, Gliocadium virens, Penicillium chrysogenum and Penicillium funiculosum. It is the particular advantage of the product, that it displays an excellent efficacy against these microorganism strains and is well tolerated by animals and human beings. This positive safety aspect makes the product highly suitable for any use leading to direct contact with the human body, like in cosmetic preparations and in the food industry.
The preparation of the cationic surfactant compounds with antimicrobial activity is described in the prior art.
The method described in ES-A-512643 is related to a first step of preparing an ester from the basic type amino acid and an alcohol and in the second step performing a condensation of the ester with a fatty acid to obtain the final product. It is a typical aspect of the method, that initially a solution of the catalyst thionyl chloride in the alcohol is prepared and that the amino acid is added to this solution. Heating of the solution is required and it takes at least 16 hours to bring the reaction to an end. The second step of the condensation is performed by adding the fatty acid as the free acid to the solution in the presence of a coupling reagent such as dicyclohexylcarbodiimide (DCDD).
An improved method has been provided in EP-A-0 749 960 which is differing from the previously mentioned method by providing in the first step a dispersion of the basic-type amino acid in alcohol and adding a catalyst like thionyl chloride to this dispersion in a drop-wise manner. It is the advantage of this adaptation of the method, that this drop-wise addition allows an excellent control of the reaction without the need of applying external heat to make the reaction run. A further difference is the performance of the second step by using a fatty acid halide. It is a particular advantage that this adaptation allows the performance of the reaction in an aqueous environment, which is a particular advantage, when the use of the final product is intended to be in the food industry. When the thionyl chloride is added, then arginine is solubilised for the formation of arginine ethyl ester dihydrochloride.
The method described in EP-A-0 749 960 is further characterised by the fact, that the second step of the condensation of the esterified amino acid is performed in an alkaline environment. EP-A-0 749 960 describes the need to perform the condensation at an alkaline pH, preferably at a pH between 8 and 10. The reason for using the alkaline environment is evidently the conviction in the art, that this type of reaction, which is a Schotten-Baumann reaction requires an alkaline environment. A comparable reaction is described in GB-A-1 352 420 which describes the reaction of arginine with a higher aliphatic acyl halide and likewise indicates the presence of an alkaline aqueous medium. A specific example contained in this prior art document indicates a pH value of 11.5–12.0 adjusted with sodium hydroxide.
The process described in EP-A-0 749 960 allows a relatively fast and efficient preparation of the wanted cationic surfactants to be used as antimicrobial products, but the inventors of the present invention have set themselves the task to continuously improve the preparative method in order to be able to produce the products industrially in the required quality in an economic manner. This continuous evaluation of improvements of the method has finally led to the present invention.